The therapeutic effect and MR molecular imaging of FA-PEG-FePt/DDP nanoliposomes in AMF on ovarian cancer.

Purpose: This study aimed to construct targeting drug-loading nanocomposites (FA-FePt/DDP nanoliposomes) to explore their potential in ovarian cancer therapy and molecular magnetic resonance imaging (MMRI). Methods: FA-FePt-NPs were prepared by coupling folate (FA) with polyethylene-glycol (PEG)-coated ferroplatinum nanoparticles and characterized. Then cisplatin (DDP) was encapsulated in FA-FePt-NPs to synthesize FA-PEG-FePt/DDP nanoliposomes by thin film-ultrasonic method and high-speed stirring, of which MMRI potential, magnetothermal effect, and the other involved performance were analyzed. The therapeutic effect of FA-FePt/DDP nanoliposomes combined with magnetic fluid hyperthermia (MFH) on ovarian cancer in vitro and in vivo was evaluated. The expression levels of Bax and epithelial-mesenchymal transition related proteins were detected. The biosafety was also preliminarily observed. Results: The average diameter of FA-FePt-NPs was about 30 nm, FA-FePt/DDP nanoliposomes were about 70 nm in hydrated particle size, with drug slow-release and good cell-specific targeted uptake. In an alternating magnetic field (AMF), FA-FePt/DDP nanoliposomes could rapidly reach the ideal tumor hyperthermia temperature (42~44 °C). MRI scan showed that FA-FePt-NPs and FA-FePt/DDP nanoliposomes both could suppress the T2 signal, indicating a good potential for MMRI. The in vitro and in vivo experiments showed that FA-FePt/DDP-NPs in AMF could effectively inhibit the growth of ovarian cancer by inhibiting cancer cell proliferation, invasion, and migration, and inducing cancer cell apoptosis, much better than that of the other individual therapies; molecularly, E-cadherin and Bax proteins in ovarian cancer cells and tissues were significantly increased, while N-cadherin, Vimentin, and Bcl-2 proteins were inhibited, effectively inhibiting the malignant progression of ovarian cancer. In addition, no significant pathological injury and dysfunction was observed in major visceras. Conclusion: We successfully synthesized FA-FePt/DDP nanoliposomes and confirmed their good thermochemotherapeutic effect in AMF and MMRI potential on ovarian cancer, with no obvious side effects, providing a favorable strategy of integrated targeting therapy and diagnosis for ovarian cancer.

Investigation of multiple nosocomial infections using a semi-Markov multi-state model.

BACKGROUND: The prevalence of multiple nosocomial infections (MNIs) is on the rise, however, there remains a limited comprehension regarding the associated risk factors, cumulative risk, probability of occurrence, and impact on length of stay (LOS). METHOD: This multicenter study includes all hospitalized patients from 2020 to July 2023 in two sub-hospitals of a tertiary hospital in Guangming District, Shenzhen. The semi-Markov multi-state model (MSM) was utilized to analyze risk factors and cumulative risk of MNI, predict its occurrence probability, and calculate the extra LOS of nosocomial infection (NI). RESULTS: The risk factors for MNI include age, community infection at admission, surgery, and combined use of antibiotics. However, the cumulative risk of MNI is lower than that of single nosocomial infection (SNI). MNI is most likely to occur within 14 days after admission. Additionally, SNI prolongs LOS by an average of 7.48 days (95% Confidence Interval, CI: 6.06-8.68 days), while MNI prolongs LOS by an average of 15.94 days (95% CI: 14.03-18.17 days). Furthermore, the more sites of infection there are, the longer the extra LOS will be. CONCLUSION: The longer LOS and increased treatment difficulty of MNI result in a heavier disease burden for patients, necessitating targeted prevention and control measures.

Association of clinical and imaging characteristics with pulmonary function testing in patients with Long-COVID.

Purpose: The purpose of this study is to identify clinical and imaging characteristics associated with post-COVID pulmonary function decline. Methods: This study included 22 patients recovering from COVID-19 who underwent serial spirometry pulmonary function testing (PFT) before and after diagnosis. Patients were divided into two cohorts by difference between baseline and post-COVID follow-up PFT: Decline group (>10 % decrease in FEV1), and Stable group (≤10 % decrease or improvement in FEV1). Demographic, clinical, and laboratory data were collected, as well as PFT and chest computed tomography (CT) at the time of COVID diagnosis and follow-up. CTs were semi-quantitatively scored on a five-point severity scale for disease extent in each lobe by two radiologists. Mann-Whitney U-tests, T-tests, and Chi-Squared tests were used for comparison. P-values <0.05 were considered statistically significant. Results: The Decline group had a higher proportion of neutrophils (79.47 ± 4.83 % vs. 65.45 ± 10.22 %; p = 0.003), a higher absolute neutrophil count (5.73 ± 2.68 × 109/L vs. 3.43 ± 1.74 × 109/L; p = 0.031), and a lower proportion of lymphocytes (9.90 ± 4.20 % vs. 21.21 ± 10.97 %; p = 0.018) compared to the Stable group. The Decline group also had significantly higher involvement of ground-glass opacities (GGO) on follow-up chest CT [8.50 (4.50, 14.50) vs. 3.0 (1.50, 9.50); p = 0.032] and significantly higher extent of reticulations on chest CT at time of COVID diagnosis [6.50 (4.00, 9.00) vs. 2.00 (0.00, 6.00); p = 0.039] and follow-up [5.00 (3.00, 13.00) vs. 2.00 (0.00, 5.00); p = 0.041]. ICU admission was higher in the Decline group than in the Stable group (71.4 % vs. 13.3 %; p = 0.014). Conclusions: This study provides novel insight into factors influencing post-COVID lung function, irrespective of pre-existing pulmonary conditions. Our findings underscore the significance of neutrophil counts, reduced lymphocyte counts, pulmonary reticulation on chest CT at diagnosis, and extent of GGOs on follow-up chest CT as potential indicators of decreased post-COVID lung function. This knowledge may guide prediction and further understanding of long-term sequelae of COVID-19 infection.

MRI-Based Prediction of Clinical Improvement Following Ventricular Shunt Placement for Normal Pressure Hydrocephalus (NPH): Development and Evaluation of an Integrated Multi-Sequence Machine Learning Algorithm.

BACKGROUND AND PURPOSE: Symptoms of normal pressure hydrocephalus (NPH) are sometimes refractory to shunt placement, with limited ability to predict improvement for individual patients. We evaluated an MRI-based artificial intelligence method to predict post-shunt NPH symptom improvement. MATERIALS AND METHODS: NPH patients who underwent magnetic resonance imaging (MRI) prior to shunt placement at a single center (2014-2021) were identified. Twelve-month post-shunt improvement in modified Rankin Scale (mRS), incontinence, gait, and cognition were retrospectively abstracted from clinical documentation. 3D deep residual neural networks were built on skull stripped T2-weighted and fluid attenuated inversion recovery (FLAIR) images. Predictions based on both sequences were fused by additional network layers. Patients from 2014-2019 were used for parameter optimization, while those from 2020-2021 were used for testing. Models were validated on an external validation dataset from a second institution (n=33). RESULTS: Of 249 patients, n=201 and n=185 were included in the T2-based and FLAIR-based models according to imaging availability. The combination of T2-weighted and FLAIR sequences offered the best performance in mRS and gait improvement predictions relative to models trained on imaging acquired using only one sequence, with AUROC values of 0.7395 [0.5765-0.9024] for mRS and 0.8816 [0.8030-0.9602] for gait. For urinary incontinence and cognition, combined model performances on predicting outcomes were similar to FLAIR-only performance, with AUROC values of 0.7874 [0.6845-0.8903] and 0.7230 [0.5600-0.8859]. CONCLUSIONS: Application of a combined algorithm using both T2-weighted and FLAIR sequences offered the best image-based prediction of post-shunt symptom improvement, particularly for gait and overall function in terms of mRS. ABBREVIATIONS: NPH = normal pressure hydrocephalus; iNPH = idiopathic NPH; sNPH = secondary NPH; AI = artificial intelligence; ML = machine learning; CSF = cerebrospinal fluid; AUROC = area under the receiver operating characteristic; FLAIR = fluid attenuated inversion recovery; BMI = body mass index; CCI = Charlson Comorbidity Index; SD = standard deviation; IQR = interquartile range.

The enzyme encoded by Myrmecia incisa, a green microalga, phospholipase A2 gene preferentially hydrolyzes arachidonic acid at the sn-2 position of phosphatidylcholine.

The enzyme phospholipase A2 (PLA2) plays a crucial role in acyl remodeling of phospholipids via the Lands' cycle, and consequently alters fatty acid compositions in triacylglycerol (TAG). In this study, a full-length cDNA sequence coding Myrmecia incisa phospholipase A2 (MiPLA2) was cloned using the technique of rapid amplification of cDNA ends. Comparison of the 1082-bp cDNA with its corresponding cloned DNA sequence revealed that MiPLA2 contained 3 introns. Mature MiPLA2 (mMiPLA2) had a conserved Ca2+-binding loop and a catalytic site motif that has been recognized in plant secretory PLA2 (sPLA2) proteins. Correspondingly, phylogenetic analysis illustrated that MiPLA2 was clustered within GroupXIA of plant sPLA2 proteins. To ascertain the function of MiPLA2, the cDNA coding for mMiPLA2 was subcloned into the vector pET-32a to facilitate the production of recombinant mMiPLA2 in Escherichia coli. Recombinant mMiPLA2 was purified and used for the in vitro enzyme reaction. Thin-layer chromatography profiles of the catalytic products generated by recombinant mMiPLA2 indicated a specificity for cleaving sn-2 acyl chains from phospholipids, thereby functionally characterizing MiPLA2. Although recombinant mMiPLA2 displayed a strong preference for phosphatidylethanolamine, it preferentially hydrolyzes arachidonic acid (ArA) at the sn-2 position of phosphatidylcholine. Results from the fused expression of p1300-sp-EGFP-mMiPLA2 illustrated that MiPLA2 was localized in the intercellular space of onion epidermis. Furthermore, the positive correlation between MiPLA2 transcription and free ArA levels were established. Consequently, the role of mMiPLA2 in the biosynthesis of ArA-rich TAG was elucidated. This study helps to understand how M. incisa preferentially uses ArA to synthesize TAG.

The Antimicrobial Peptide Tilapia Piscidin 4 Induced the Apoptosis of Bladder Cancer Through ERK/SIRT1/PGC-1α Signaling Pathway.

Marine antimicrobial peptides have been demonstrated in numerous studies to possess anti-cancer properties. This research investigation aimed to explore the fundamental molecular mechanisms underlying the antitumor activity of Tilapia piscidin 4 (TP4), an antimicrobial peptide, in human bladder cancer. TP4 exhibited a remarkable inhibitory effect on the proliferation of bladder cancer cells through cell cycle arrest at the G2/M phase. Additionally, TP4 upregulated the expression of cleaved caspase-3, caspase-9, and PARP, leading to the activation of apoptotic pathways in bladder cancer cells. TP4 exhibit a marked rise in mitochondria reactive oxygen species, leading to the subsequent loss of potential for the mitochondrial membrane. Furthermore, the inhibition of mitochondrial oxidative phosphorylation resulted in a decrease in downstream ATP production. Meanwhile, TP4-treated bladder cancer cells showed an increase in Bax and ERK but a decrease in SIRT1, PGC-1α, and Bcl2. ERK activation, SIRT1/PGC-1α-axis, and TP4-induced apoptosis were all significantly reversed by the ERK inhibitor SCH772984. Finally, the inhibitory effect of TP4 on tumor growth has been confirmed in a zebrafish bladder cancer xenotransplantation model. These findings suggest that TP4 may be a potential agents for human bladder cancer through apoptosis induction, ERK activation, and the promotion of SIRT1-mediated signaling pathways.

Correction: Halogen-bonded charge-transfer co-crystal scintillators for high-resolution X-ray imaging.

[This corrects the article DOI: 10.1039/D4SC00735B.].

Halogen-bonded charge-transfer co-crystal scintillators for high-resolution X-ray imaging.

The development of high-quality organic scintillators encounters challenges primarily associated with the weak X-ray absorption ability resulting from the presence of low atomic number elements. An effective strategy involves the incorporation of halogen-containing molecules into the system through co-crystal engineering. Herein, we synthesized a highly fluorescent dye, 2,5-di(4-pyridyl)thiazolo[5,4-d]thiazole (Py2TTz), with a fluorescence quantum yield of 12.09%. Subsequently, Py2TTz was co-crystallized with 1,4-diiodotetrafluorobenzene (I2F4B) and 1,3,5-trifluoro-2,4,6-triiodobenzene (I3F3B) obtaining Py2TTz-I2F4 and Py2TTz-I3F3. Among them, Py2TTz-I2F4 exhibited exceptional scintillation properties, including an ultrafast decay time (1.426 ns), a significant radiation luminescence intensity (146% higher than Bi3Ge4O12), and a low detection limit (70.49 nGy s-1), equivalent to 1/78th of the detection limit for medical applications (5.5 µGy s-1). This outstanding scintillation performance can be attributed to the formation of halogen-bonding between I2F4B and Py2TTz. Theoretical calculations and single-crystal structures demonstrate the formation of halogen-bond-induced rather than π-π-induced charge-transfer cocrystals, which not only enhances the X-ray absorption ability and material conductivity under X-ray exposure, but also constrains molecular vibration and rotation, and thereby reducing non-radiative transition rate and sharply increasing its fluorescence quantum yields. Based on this, the flexible X-ray film prepared based on Py2TTz-I2F4 achieved an ultrahigh spatial resolution of 26.8 lp per mm, underscoring the superiority of this strategy in developing high-performance organic scintillators.

Nobiletin derivative, 5-acetoxy-6,7,8,3',4'-pentamethoxyflavone, inhibits neuroinflammation through the inhibition of TLR4/MyD88/MAPK signaling pathways and STAT3 in microglia.

OBJECTIVE: Microglia in the central nervous system regulate neuroinflammation that leads to a wide range of neuropathological alterations. The present study investigated the anti-neuroinflammatory properties of nobiletin (Nob) derivative, 5-acetoxy-6,7,8,3',4'-pentamethoxyflavone (5-Ac-Nob), in lipopolysaccharide (LPS)-activated BV2 microglia. MATERIALS AND METHODS: By using the MTT assay, Griess method, flow cytometry, and enzyme-linked immunosorbent assay (ELISA), we determined the cell viability, the levels of nitric oxide (NO), reactive oxygen species (ROS), and pro-inflammatory factors (interleukin 1 beta; IL-1ß, interleukin 6; IL-6, tumor necrosis factor alpha; TNF-α and prostaglandin E2; PGE2) in LPS-stimulated BV2 microglia. Toll-like receptor 4 (TLR4)-mediated myeloid differentiation primary response gene 88 (MyD88)/nuclear factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK) signaling pathway and signal transducer and activator of transcription 3 (STAT3) were measured by western blotting. Analysis of NO generation and mRNA of pro-inflammatory cytokines was confirmed in the zebrafish model. RESULTS: 5-Ac-Nob reduced cell death, the levels of NO, ROS, inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), and pro-inflammatory factors in LPS-activated BV-2 microglial cells. TLR4-mediated MyD88/NF-κB and MAPK pathway (p38, ERK and JNK) after exposure to 5-Ac-Nob was also suppressed. Moreover, 5-Ac-Nob inhibited phosphorylated STAT3 proteins expression in LPS-induced BV-2 microglial cells. Furthermore, we confirmed that 5-Ac-Nob decreased LPS-induced NO generation and mRNA of pro-inflammatory cytokines in the zebrafish model. CONCLUSIONS: Our findings suggest that 5-Ac-Nob represses neuroinflammatory responses by inhibiting TLR4-mediated signaling pathway and STAT3. As a result of these findings, 5-Ac-Nob has potential as an anti-inflammatory agent against microglia-mediated neuroinflammatory disorders.

IL-33 in patients with periodontitis and chronic obstructive pulmonary disease.

OBJECTIVE: A link between periodontitis and chronic obstructive pulmonary disease (COPD) has been identified, and interleukin-33 (IL-33) may play an important role in the common inflammatory mechanisms of these diseases. This study analyzed the associations of the serum IL-33 level with the occurrence and severity of periodontitis and COPD. METHODS: A total of 161 participants were divided into four groups: healthy volunteers, periodontitis patients, COPD patients, and patients with both COPD and periodontitis. Associations between serum IL-33 levels were measured by enzyme-linked immunosorbent assay, and clinical factors as well as the risks and severity of periodontitis and COPD were analyzed. RESULTS: Serum IL-33 levels were lower in all patient groups than in healthy controls. A trend toward lower IL-33 levels was observed among patients with both diseases compared with patients with either disease alone. The serum IL-33 level was also inversely associated with the severity of periodontitis and COPD. The serum IL-33 level was negatively associated with risks of periodontitis and COPD, indicating that IL-33 is likely involved in the pathophysiologic mechanism of the relationship between COPD and periodontitis. CONCLUSION: This study advances our understanding of the association between COPD and periodontitis and provides new bases for COPD prevention and treatment.

Highly intense NIR emissive Cu4Pt2 bimetallic clusters featuring Pt(i)-Cu4-Pt(i) sandwich kernel.

Metal nanoclusters (NCs) capable of near-infrared (NIR) photoluminescence (PL) are gaining increasing interest for their potential applications in bioimaging, cell labelling, and phototherapy. However, the limited quantum yield (QY) of NIR emission in metal NCs, especially those emitting beyond 800 nm, hinders their widespread applications. Herein, we present a bright NIR luminescence (PLQY up to 36.7%, ∼830 nm) bimetallic Cu4Pt2 NC, [Cu4Pt2(MeO-C6H5-C[triple bond, length as m-dash]C)4(dppy)4]2+ (dppy = diphenyl-2-pyridylphosphine), with a high yield (up to 67%). Furthermore, by modifying the electronic effects of R in RC[triple bond, length as m-dash]C- (R = MeO-C6H5, F-C6H5, CF3-C6H5, Nap, and Biph), we can effectively modulate phosphorescence properties, including the PLQY, emission wavelength, and excited state decay lifetime. Experimental and computational studies both demonstrate that in addition to the electron effects of substituents, ligand modification enhances luminescence intensity by suppressing non-radiation transitions through intramolecular interactions. Simultaneously, it allows the adjustment of emitting wavelengths by tuning the energy gaps and first excited triplet states through intermolecular interactions of ligand substituents. This study provides a foundation for rational design of the atomic-structures of alloy metal NCs to enhance their PLQY and tailor the PL wavelength of NIR emission.

Rosmarinic acid Ameliorates neuronal regeneration in the bridging silicone rubber conduits of the sciatic nerve in taxol-treated rats.

Background and aim: Taxol modulates local inflammatory conditions in peripheral nerves, which may impair their regeneration and recovery when injured. This study aimed to determine the effects of rosmarinic acid (RA, a polyphenol constituent of many culinary herbs) on the regeneration of the sciatic nerves in the bridging conduits. Experimental procedure: In the cell study, RA decreased nuclear factor (NF)-κB activity induced by taxol in a dose dependency. In the animal model, taxol-treated rats were divided into 3 groups (n = 10/group): taxol (2 mg/kg body weight for 4 times) and taxol + RA (3 times/week for 4 weeks at 20 and 40 mg/kg body weight) groups. Macrophage infiltration, calcitonin gene-related peptide (CGRP) expression levels, neuronal connectivity, animal behavior, and neuronal electrophysiology were evaluated. Results and conclusion: At the end of 4 weeks, macrophage density, CGRP expression level, and axon number significantly increased in the RA group compared with the taxol group. The RA administration unaffected heat, cold plate licking latencies, and motor coordination. Moreover, the 40 mg/kg RA group had significantly larger nerve conduction velocity and less latency compared to the taxol group. This study suggested that RA could ameliorate local inflammatory conditions to augment the recovery of regenerating nerves by accelerating their regrowth and improving electrophysiological function in taxol-treated peripheral nerve injury repaired with the silicone rubber conduit.

Carbon Nanofiber Membranes Loaded with MXene@g-C3N4: Preparation and Photocatalytic Property.

In this study, a Ti3C2 MXene@g-C3N4 composite powder (TM-CN) was prepared by the ultrasonic self-assembly method and then loaded onto a carbon nanofiber membrane by the self-assembly properties of MXene for the treatment of organic pollutants in wastewater. The characterization of the TM-CN and the C-TM-CN was conducted via X-ray diffraction (XRD), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and Fourier transform infrared spectrometer (FTIR) to ascertain the successful modification. The organic dye degradation experiments demonstrated that introducing an appropriate amount of Ti3C2 MXene resulted in the complete degradation of RhB within 60 min, three times the photocatalytic efficiency of a pure g-C3N4. The C-TM-CN exhibited the stable and outstanding photocatalytic degradation of the RhB solution over a wide range of pH values, indicating the characteristics of the photodegradation of organic pollutants in a wide range of aqueous environments. Furthermore, the results of the cyclic degradation experiments demonstrated that the C-TM-CN composite film maintained a degradation efficiency of over 85% after five cycles, thereby confirming a notable improvement in its cyclic stability. Consequently, the C-TM-CN composite film exhibits excellent photocatalytic performance and is readily recyclable, making it an auspicious eco-friendly material in water environment remediation.

Diet Outcome in Patients With Hypopharyngeal Defects Repaired With Different Reconstruction Flaps: A Comparative Study.

OBJECTIVES: To assess potential risk factors influencing diet outcomes after reconstruction of subtotal hypopharyngeal defects using free patch- or tube-shaped anterolateral thigh (ALT) fasciocutaneous flaps. STUDY DESIGN: Retrospective cohort study. SETTING: First-level referral hospital. METHODS: Between January 2011 and December 2020, we studied hypopharyngeal cancer patients who underwent the reconstruction of hypopharyngeal defects using free patch- or tube-shaped ALT fasciocutaneous flaps. The choice between patch- or tube-shaped ALT flaps depended on the defect's nature, favoring patch-shaped for subtotal defects and tube-shaped for circumferential defects. A restricted diet was characterized by a history of enterostomy or endoscopic esophageal dilation treatment postreconstruction. We analyzed patients with restricted diets at 1- and 3-year follow-up visits. RESULTS: Ninety-eight patients were enrolled; 39 patch-shaped flaps, and 59 tube-shaped flaps. No significances were noted in demographics, postoperative radiotherapy (RT) or chemotherapy, rates of free flap reoperation/salvage, or complications. However, a significant difference emerged in diet outcomes at the 1-year follow-up (P = .005). The rate of a restricted diet was 6.08 times higher in patients with tube-shaped flaps compared to patch-shaped flaps (95% confidence interval [CI]: 1.95-18.94). Stratifying based on postoperative RT revealed a 5.47 times higher rate of a restricted diet in tube-shaped flap recipients compared to patch-shaped flap recipients (95% CI: 1.44-20.48). No significances were observed in 5-year survival rates. CONCLUSION: Concerning postoperative RT, patch-shaped flaps exhibited a lower incidence of a restricted diet compared to tube-shaped flaps. Preservation of the posterior mucosa may play a crucial role in preventing RT-induced esophageal stricture.

Mobile Apps for Patients with Peritoneal Dialysis: Systematic App Search and Evaluation.

BACKGROUND: Peritoneal dialysis (PD) is one type of renal replacement therapy. If patients have problems during the dialysis process, healthcare providers may not be able assist the patients immediately. mHealth can provide patients with information and help them to solve problems in real-time, potentially increasing their willingness to choose PD. OBJECTIVE: The objectives of this study were to conduct a comprehensive review of free mobile applications for patients with PD on the Internet and to recommend suitable mobile applications to facilitate patient self-management and health. METHODS: We conducted a systematic search for PD mobile applications on Google Play and the Apple iTunes Store from 3 to 16 June 2023. RESULTS: A total of 828 identifiable mobile applications were initially identified, and ultimately, 21 met the inclusion criteria. The Mobile App Rating Scale (MARS) assessment of the applications revealed the highest score in the functionality domain, followed by the aesthetics, information, app-specific, subjective quality, and engagement domains, respectively. In the comprehensive self-management of PD, the highest percentage was related to disease-related information. CONCLUSION: The findings of this study suggest that some applications, with the highest quality, can be recommended to patients for use in English or traditional Chinese.

Staphylococcus aureus foldase PrsA contributes to the folding and secretion of protein A.

BACKGROUND: Staphylococcus aureus secretes a variety of proteins including virulence factors that cause diseases. PrsA, encoded by many Gram-positive bacteria, is a membrane-anchored lipoprotein that functions as a foldase to assist in post-translocational folding and helps maintain the stability of secreted proteins. Our earlier proteomic studies found that PrsA is required for the secretion of protein A, an immunoglobulin-binding protein that contributes to host immune evasion. This study aims to investigate how PrsA influences protein A secretion. RESULTS: We found that in comparison with the parental strain HG001, the prsA-deletion mutant HG001ΔprsA secreted less protein A. Deleting prsA also decreased the stability of exported protein A. Pulldown assays indicated that PrsA interacts with protein A in vivo. The domains in PrsA that interact with protein A are mapped to both the N- and C-terminal regions (NC domains). Additionally, the NC domains are essential for promoting PrsA dimerization. Furthermore, an immunoglobulin-binding assay revealed that, compared to the parental strain HG001, fewer immunoglobulins bound to the surface of the mutant strain HG001ΔprsA. CONCLUSIONS: This study demonstrates that PrsA is critical for the folding and secretion of protein A. The information derived from this study provides a better understanding of virulent protein export pathways that are crucial to the pathogenicity of S. aureus.

Oscillatory correlates of threat imminence during virtual navigation.

The Predatory Imminence Continuum Theory proposes that defensive behaviors depend on the proximity of a threat. While the neural mechanisms underlying this proposal are well studied in animal models, it remains poorly understood in humans. To address this issue, we recorded EEG from 24 (15 female) young adults engaged in a first-person virtual reality Risk-Reward interaction task. On each trial, participants were placed in a virtual room and presented with either a threat or reward conditioned stimulus (CS) in the same room location (proximal) or different room location (distal). Behaviorally, all participants learned to avoid the threat-CS, with most using the optimal behavior to actively avoid the proximal threat-CS (88% accuracy) and passively avoid the distal threat-CS (69% accuracy). Similarly, participants learned to actively approach the distal reward-CS (82% accuracy) and to remain passive to the proximal reward-CS (72% accuracy). At an electrophysiological level, we observed a general increase in theta power (4-8 Hz) over the right posterior channel P8 across all conditions, with the proximal threat-CS evoking the largest theta response. By contrast, distal cues induced two bursts of gamma (30-60 Hz) power over midline-parietal channel Pz (200 msec post-cue) and right frontal channel Fp2 (300 msec post-cue). Interestingly, the first burst of gamma power was sensitive to the distal threat-CS and the second burst at channel Fp2 was sensitive to the distal reward-CS. Together, these findings demonstrate that oscillatory processes differentiate between the spatial proximity information during threat and reward encoding, likely optimizing the selection of the appropriate behavioral response.

Parametric Analysis of Donor Activation for Glycosylation Reactions.

The chemical synthesis of complex oligosaccharides relies on efficient and highly reproducible glycosylation reactions. The outcome of a glycosylation is contingent upon several environmental factors, such as temperature, acidity, the presence of residual moisture, as well as the steric, electronic, and conformational aspects of the reactants. Each glycosylation proceeds rapidly and with a high yield within a rather narrow temperature range. For better control over glycosylations and to ensure fast and reliable reactions, a systematic analysis of 18 glycosyl donors revealed the effect of reagent concentration, water content, protecting groups, and structure of the glycosyl donors on the activation temperature. With these insights, we parametrize the first step of the glycosylation reaction to be executed reliably and efficiently.

Synthesis, characterization, and efficacy evaluation of a PH-responsive Fe-MOF@GO composite drug delivery system for the treating colorectal cancer.

Luteolin is a potent anti-colorectal cancer chemical. However, its effectiveness is hindered by its poor solubility in water and fat, and it is easy to degrade by gastrointestinal enzymes. In this study, a nano-composite carrier, NH2-MIL-101(Fe)@GO (MG), based on aminated MIL-101(Fe) and graphene oxide (GO) was developed and evaluated. This carrier co-delivered luteolin and matrine, while marine was used to balance the pH for the nano-preparation. The loading capacities for luteolin and matrine were approximately 9.8% and 14.1%, respectively. Luteolin's release at pH = 5 was significantly higher than at pH = 7.4, indicating it had an acidic pH response release characteristic. Compared to MOF and GO alone, MG and NH2-MIL-101(Fe)@GO@Drugs (MGD) enhanced anti-cancer activity by inhibiting tumor cell migration, increasing ROS generation, and upregulating the expression of Caspase-3 and Caspase-9. In conclusion, this study contributes new ideas and methods to the treatment strategy of multi-component anti-colorectal cancer therapy. It also advances drug delivery systems and supports the development of more effective and targeted treatment approaches for colorectal cancer.